The standard search strategy of the Cochrane Neonatal Review Group was used. The review was updated with searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2006), MEDLINE (1966-March 2006), EMBASE (1980-March 2006) and CINAHL (1982-March 2006) and previous reviews including cross references.
SELECTION CRITERIA: Randomised and quasi-randomised trials that compare the use of a hydrolysed infant formula to human milk or cow's milk formula. Trials with >80% follow up of participants were eligible for inclusion.
DATA COLLECTION AND ANALYSIS: Two trials compared early, short term hydrolysed formula to human milk feeding. No significant difference in infant
allergy or childhood
cow's milk allergy (CMA) were reported. No eligible trial compared prolonged hydrolysed formula to human milk feeding. Two trials compared early, short term hydrolysed formula to cow's milk formula feeding. No significant benefits were reported. One large quasi-random study reported a reduction in infant CMA of borderline significance in low risk infants (RR 0.62, 95% CI 0.38, 1.00). Ten eligible studies compared prolonged feeding with hydrolysed formula versus cow's milk formula in high risk infants. Meta-analysis found a significant reduction in infant
allergy (seven studies, 2514 infants; typical RR 0.79, 95% CI 0.66, 0.94), but not in the incidence of childhood
allergy (two studies, 950 infants; typical RR 0.85, 95% CI 0.69, 1.05). There was no significant difference in infant
eczema (eight studies, 2558 infants, typical RR 0.84, 95% CI 0.68, 1.04), childhood
eczema incidence (two studies, 950 infants, typical RR 0.83, 95% CI 0.63, 1.10), childhood
eczema prevalence (one study, 872 infants; RR 0.66, 95% CI 0.43, 1.02), or infant or childhood
asthma,
rhinitis and
food allergy. One study reported a significant reduction in infants with CMA with confirmed atopy (RR 0.36, 95% CI 0.15, 0.89). Subgroup analysis of trials blinded to formula found no significant difference in infant
allergy (four studies, 2156 infants; typical RR 0.87, 95% CI 0.69, 1.08) or childhood
allergy incidence (one study, 872 infants; RR 0.91, 95% CI 0.73, 1.14). No eligible trial examined the effect of prolonged hydrolysed formula feeding on
allergy beyond early childhood. There is evidence that preterm or low
birthweight infants fed a hydrolysed preterm formula have significantly reduced
weight gain, but not in other growth parameters (head circumference or length). Studies in term infants report no adverse effects on growth. Subgroup analysis of trials of partially hydrolysed versus cow's milk formula found a significant reduction in infant
allergy (six studies, 1391 infants; typical RR 0.79, 95% CI 0.65, 0.97) but not childhood
allergy, or infant or childhood
asthma,
eczema or
rhinitis. Methodological concerns were the same as for the overall analysis. Analysis of trials of extensively hydrolysed formula versus cow's milk formula found no significant differences in
allergy or
food intolerance. Infants fed extensively hydrolysed formula compared with partially hydrolysed formula had a significant reduction in
food allergy (two studies, 341 infants; typical RR 0.43, 95% CI 0.19, 0.99), but there was no significant difference in all
allergy or any other specific
allergy incidence. Comparing extensively hydrolysed
casein containing formula with cow's milk formula, one study (431 infants) reported a significant reduction in childhood
allergy incidence (RR 0.72, 95% CI 0.53, 0.97). Meta-analysis found a significant reduction in infant
eczema (three studies, 1237 infants; typical RR 0.71, 95% CI 0.51, 0.97). One study reported a significant reduction in childhood
eczema incidence (RR 0.66, 95% CI 0.44, 0.98) and prevalence (RR 0.50, 95% CI 0.27, 0.92).
AUTHORS' CONCLUSIONS: